Do Atypical Antipsychotics Cause Stroke?
- 243 Downloads
Post hoc analyses of pooled results from 11 randomised controlled trials of risperidone and olanzapine in elderly dementia subjects revealed an increased incidence of cerebrovascular adverse events compared with placebo. Reanalysis of the risperidone trials suggests that some of the increased incidence may be accounted for by nonspecific events that were not strokes. Large observational administrative health database studies appear to confirm that risperidone and olanzapine are not associated with an increased risk of stroke in elderly patients compared with typical antipsychotics or untreated dementia patients. A larger number of subjects with vascular and mixed dementias were included in the risperidone studies compared with the olanzapine studies, which likely accounts for the increased incidence of cerebrovascular adverse events in the risperidone trials compared with the olanzapine studies. Potential mechanisms proposed to explain an association between atypical antipsychotics and cerebrovascular adverse events include thromboembolic effects, cardiovascular effects (e.g. orthostatic hypotension, arrhythmias), excessive sedation resulting in dehydration and haemoconcentration, and hyperprolactinaemia. However, there is little evidence to support these hypothesised mechanisms at present. The association between atypical antipsychotics and cerebrovascular adverse events requires further clarification. At the present time, this association is another factor that clinicians should consider when weighing the risks and benefits of treating behavioural and psychological disturbances in elderly dementia patients.
KeywordsRisperidone Olanzapine Atypical Antipsychotic Typical Antipsychotic Stroke Risk Factor
No pharmaceutical company support was received for this paper. Drs Herrmann and Lanctôt have previously received research support and speakers’ honoraria from Janssen Ortho Inc., Eli Lilly, Novartis, Pfizer, AstraZeneca, all manufacturers of atypical antipsychotics. The authors wish to acknowledge Dr Andrew Greenspan of Janssen Medical Affairs, LLC for providing data on file for risperidone, and Dr Jamie Karagianis of Eli Lilly Canada for providing data on file for olanzapine.
- 4.Doody RS, Stevens JC, Beck C, et al. Practice parameter: management of dementia (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2001; 56: 1154–66Google Scholar
- 5.Committee on Safety of Medicines. Summary of clinical trial data on cerebrovascular adverse events (CVAEs) in randomized clinical trials of risperidone conducted in patients with dementia [online]. Available from URL: http://www.mca.gov.uk/aboutagency/regframework/csm/csmhome.htm [Accessed 2004 Jun 28]
- 6.Review Manager (Rev Man) [computer programme]. Version 4.2 for Windows. Oxford: The Cochrane Collaboration, 2002Google Scholar
- 9.Greenspan A, Eerdekens M, Mahmoud R. Is there an increased risk of cerebrovascular adverse events among dementia patients treated with risperidone? Proceedings of the Annual Meeting of the International College of Geriatric Psychoneuropharmacology; 2003 Dec 12–14; San JuanGoogle Scholar
- 10.Greenspan A, Eerdekens M, Mahmoud R. Is there an increased rate of cerebrovascular adverse events with risperidone in patients with dementia? [abstract]. Int J Neuropsychopharmacol 2004; 7Suppl. 1: S205Google Scholar
- 14.Data on file, Janssen, 2004Google Scholar
- 15.Cavazzoni P, Young C, Polzer J, et al. Incidence of cerebrovascular adverse events and mortality during antipsychotic clinical trials of elderly patients with dementia. Proceedings of the 44th Annual New Clinical Drug Evaluation Unit; 2004 Jun 1-4; PhoenixGoogle Scholar
- 16.Data on file, Eli Lilly, 2004Google Scholar
- 22.American Association of Geriatric Psychiatry. What to consider in evaluating evidence: the case of the risperidone warning: an AAGP teleconference [online]. Available from URL: http://www.aagpgpa.org/members/risperidone.asp [Accessed 2004 May 31]
- 37.Liperoti R, Gambassi G, Lapane K, et al. Cerebrovascular events among elderly patients treated with conventional or atypical antipsychotics. Proceedings of the Annual Meeting of the American Geriatrics Society; 2004 May 17–21; Las VegasGoogle Scholar
- 38.Kozma C, Engelhart L, Long S, et al. No evidence for relative stroke risk in elderly dementia patients treated with risperidone versus other antipsychotics. Proceedings of the Annual Meeting of the American Psychiatric Association; 2004 May 1–6; New YorkGoogle Scholar
- 44.Merrian AE, Aronson MK, Gaston P, et al. The psychiatric symptoms of Alzheimer’s disease. J Am Geriatr Soc 1988; 36: 7–12Google Scholar
- 47.Schneider L, Dagerman K. Meta-analysis of atypical antipsychotics for dementia patients balancing efficacy and adverse events. Int Psychogeriatr 2003; 15(2 Suppl.): 164–5Google Scholar